Peripheral arterial disease (PAD) is common condition, particularly in the elderly, but is the least frequently studied and the least well understood of the major atherosclerotic diseases. Two separate and distinct PAD studies are proposed. The first study, the VA Patient Study, will examine the progression of PAD in a cohort of patients diagnosed as having large vessel PAD (LV-PAD) or isolated small vessel PAD (ISV-PAD) at the San Diego VA Medial Center from July, 1984 to June, 1989 (LV-PAD n=600, ISV-PAD n=150). The four non-invasive tests for PAD used in the initial diagnosis will be repeated after an average interval of 5 years. These tests are segmental blood pressure, flow velocity by Doppler ultrasound, post- occlusive reactive hyperemia, and pulse reappearance time. We will examine the proportion of patients who worsen, stay unchanged, or improve for both LV-PAD and ISV-PAD, and which risk factors are related to PAD progression or regression. Risk factors to be examined include cigarette smoking, alcohol consumption, lipids and lipoproteins, blood pressure, fasting plasma glucose, diabetes history, immunoglobulin E, and creatinine. Recent work had highlighted the potential importance of these latter 2 factors. Changes in PAD symptoms will be analyzed. We will also evaluate the degree of concordance between PAD and carotid disease, utilizing phonoangiography for non-invasive assessment of the carotid circulation. The second study, the Community Follow-up, will follow-up subjects with and without PAD from our previous PAD study cohort (n=624,69 with LV-PAD, 90 with ISV-PAD), to determine the associations of LV-PAD and ISV-PAD with subsequent CHD and CVD morbidity and mortality. These subjects had non- invasive testing for PAD in 1978-1981, and have been followed for morbidity and mortality since. The VA Patient Study in a clinical population will provide a large number of cases of LV-PAD and ISV-PAD to address in detail questions concerning the natural history and progression of PAD. The population based nature of the Community Follow-up and the long follow-up time will allow evaluation of the prognostic significance of a broad spectrum of PAD. To our knowledge, this proposal to evaluate the natural history of PAD in separate studies in a clinical and a general population is unique.